Mandip Dhamoon, MD, MPH is an Assistant Professor of Neurology at the Mount Sinai School of Medicine (MSSM) and a Dr. PH candidate in epidemiology at Columbia University. He has performed several research projects in stroke epidemiology with the Northern Manhattan Study (NOMAS) resulting in multiple first-author publications. His immediate goals are to gain the skills needed to perform longitudinal analysis of repeated functional and quality of life (QOL) measures and to model the course of these outcomes before and after stroke. His long-term career goals are to become an independently funded academic neurologist and epidemiologist with expertise in the prediction of functional status over time in population. Environment: Using resources and mentors from MSSM and Columbia University, Dr. Dhamoon will obtain statistical expertise through coursework and mentorship with Dr. Bagiella, a senior biostatistician at MSSM. He will also gain facility with measures of functional status and QOL under the mentorship of experienced trialist, data manager, and epidemiologist Dr. Markowitz. He will continue learning about the design and analysis of large epidemiological datasets by working on NOMAS and through mentorship with Dr. Elkind. Seminars and annual conferences and meetings will complete his training plan. Research: The objective of this proposal is to identify individuals at risk of steep decline in functional status and QOL, and to describe the long-term trajectory of these outcomes before and after major vascular events. Our central hypotheses are that stroke can cause a decline in function and QOL over the long term even in the absence of recurrent vascular events, and that vascular risk factors and inflammatory and imaging markers predict an accelerated decline. To enhance validity, we will study these hypotheses in two large observational cohorts, NOMAS and the Cardiovascular Health Study (CHS). The hypotheses for this proposal are: Hypothesis #1: The following factors independently predict worse functional status and QOL in NOMAS in those free of stroke at baseline: a) serum inflammatory biomarkers; and b) cerebral white matter disease. Hypothesis #2: The slope of decline in functional status and QOL over the long term is steeper after stroke than before stroke. The slope of decline before and after myocardial infarction (MI) does not change. Hypothesis #3: NOMAS has several unique strengths, but its measures of functional status and QOL are limited, and this Aim is intended to interpret results according to more modern and applicable scales. We will collect the Frenchay Activities Index (FAI), modified Rankin scale (MRS), and the Short Form Health Survey (SF-12) in all patients returning for follow-up assessments. We hypothesize that there is moderate agreement between the FAI, BI, and the MRS in NOMAS, primarily due to ceiling and floor effects of the BI. There is high agreement between the SF-12 and QLI.